The relationships between increased polyol pathway activity, increased water content and impaired respiration in aortic tissue incubated with elevated glucose concentrations and associated changes in the metabolism of free myoinositol will be determined. Myoinositol synthesis from glucose, the release of free myoinositol into the medium, and the incorporation of newly synthesized myoinositol into phosphoinositides will be determined in tissue incubated with low and high glucose concentrations, and in the presence of known inhibitors of aortic aldose reductase. A preparation of isolated smooth muscle cells from rabbit aorta will be developed and utilized to determine the extent to which the effects of high glucose concentrations observed in whole aorta reflect changes in aortic smooth muscle cells. Studies of the composition of glomerular basement membrane of normal and streptozotocin diabetic rats will be carried out to determine whether changes in composition similar to those observed in human diabetics can be induced. Methods for the determination of acetone in plasma and cerebrospinal fluid will be developed to determine whether the degree of unconsciousness in such patients correlates with the presence of elevated plasma or CSF acetone.